Acute and chronic hepatitis

Viral hepatitis is a group systemic infection affecting the liver predominantly caused by 5 kinds of viruses at least Viral hepatitis may be divided into 5 types according to etiology, that is hepatitis A, B, C, D and E Although the agents can be distinguished by its antigenic properties, the 5 kinds of viruses may produce clinical similar illness Clinical manifestations are characterized by anorexia, nausea, lassitude, enlarged liver and abnormal liver function, a part of cases may appear jaundice. Subclinical infection is common Hepatitis A and E shows acute hepatitis, hepatitis B, C and D predispose to a chronic hepatitis and is related to liver cirrhosis and hepatic cancer The course of acute hepatitis is about 2-4 months generally. Recently, 2 kinds of viruses named HGV and TTV are discovered and considered to relate to viral hepatitis

Epidemiology
Susceptibility and immunity of population
Hepatitis A
Most adult has anti-HAV due to covert infection. Infent under 6 month acquired antibody from mother. Young children is susceptible

Hepatitis B
Infents are susceptible to HB after boring .HBV infection developed in infents children and teenages

Hepatitis C
Population is common susceptible. Anti-HCV is not protective antibody.

Hepatitis D
Common susceptible

Hepatitis E
Common susceptible Children appear covert infection, adult show overt infection

Epidemic feature
Sporadic occurrence Hepatitis A:sporadic occurrence may be seen in developing countries of high epidemic area Hepatitis B:sporadic occurrence is a major mode of onset for HB ,there is a family clustering phenomenon which is related with vertical infection Hepatitis C:non-transfusion HC is called sporadic HC by mother to infant or life CONTACTTRASMISSION Hepatitis E:in non-epidemic area, HE is sporadic occurrence

Outbreak epidemic Due to food and water are contaminated lead to outbreak
of HA and HE

Seasonal distribution HA: most cases developed in autumn and winter HE: most cases developed in summer and autumn

Pathogenesis
Hepatitis A:
HAV invade into human body by mouth and cause viremia. After one week, the HAV reach liver cells replicate within. Then enter intestine appear in feces. HBV invade into the human body by skin and mucosa, via blood flow enter the liver and other organs such as pancreas, bill duct, vessels, WBC, bone marrow, glomerular basement membranes HBV invade into the human body by skin and mucosa, via blood flow enter the liver and other organs such as pancreas, bille duct, vessels, WBC, bone marrow, glomerular basement membranes HBcAg, HBsAg, HBeAg and HLA-appear on the liver cells infected with are recognized by CTL simultaneously and lead to the cytolysis of liver cells

Hepatitis B:

 Pathology

Degeneration Necrosis Regeneration Infiltration of inflammatory cells Hyperplasia of interstitial cells

Acute viral hepatitis

The degeneration of liver cells include ballooning degeneration, fatty degeneration, acidophilic degeneration Cell nucleus vacuolar degeneration Focal or spotty necrosis and regeneration The infiltration of mononuclear cell, plasmocyte ,lymphocyte in portal area Cholestasis and form of bile thrombus in bile capillaries of liver Piecemeal necrosis

Chronic viral hepatitis

Mild chronic hepatitis G 1-2, S 0-2
Degeneration, spotty, focal necrosis, acidophilic body Portal may have or no the infiltration of inflammation cell, mild PN or enlarged The structure is intact

Moderate chronic hepatitis (CAH)

Portal area have obvious inflammation, with moderate PN Severe inflammation with BN of intralobule Form fibrous septum, most the structure of lobule reserved Portal area has severe inflammation with severe PN BN of extensive range involving several lobules Much more fibrous septum distortion of lobule structure or form early liver cirrhosis

Severe chronic hepatitis

Fulminant viral hepatitis (hepatitis gravis)

Acute hepatitis gravis: liver cells show massive necrosis including great among of liver cells. Necrosis and reticular fiber network collapse, so the liver is greatly reduce in size-acute yellow hepatic atrophy Except massive necrosis, there are ball-like regeneration of liver cells New connective tissue which form fibrous band and separate the liver cells regenerated forming pseudolobuli Bile capillaries hyperplasia

Subacute hepatitis gravis

Chronic hepatitis gravis:

Based on the pathologic changes of chronic hepatitis or liver cirrhosis, there are massive or sub massive necrosis of liver cells

Cholestatic viral hepatitis There are the changes of acute hepatitis There is obvious cholestasis In severe cases, the liver cells may appear glandular duct
like Portal area shows edema and small bile duct is dilation

Pathophysiology
Jaundice is mainly hepatocytic jaundice and obstructive jaundice Hepatic encephalopathy

Retention of toxic material lead to poisoning of CNS Imbalance of aminoacid False neurotransmitter hypothesis Other evoked factors Deficiency of many kinds of blood coagulating factors, DIC, thrombocytopenia lead to hemorrhage

Hemorrhage

Acute renal failure (hepatic-renal syndrome) Hepatopulmonary syndrome

Ascites

Clinical manifestation
Incubation period

HA HB HC HD HE

15-45 days 30-180 days 15-150 days similar to HB 10-70 days

30 days 70 days 50 days 40 days

Clinical types

Acute viral hepatitis

Acute icteric viral hepatitis Acute anicteric viral hepatitis

Acute viral hepatitis Acute icteric viral hepatitis the cause may be 2-4 months and
divided three periods

Preicteric period In HA, HE, the onset is abrupt with fever; but HB, HC, the onset is
insidious. The initial symptoms: loss of appetite, nausea, vomiting lassitude, abdominal pain and diarrhea. The end of the period, the urine darkens. A few patients, especial children, fever, headache, upper respiratory tract symptome are main manifestations The duration of this period varies from 1-21 days, average 5-7 days

Icteric period
The urine deepens continuously and jaundice appears on the skin and sclera within 2 weeks Subjective symptoms is abate Pruritus may appear about 1 week Liver palpable 7%, spleen palpable 20% The period lasts 2-6 weeks

Convalescent period
The jaundice disappear gradually, symptoms abate or disappear Liver and spleen retract, liver function return to normal The period lasts 2 weeks to 4 months, average 1 month About 10% of HB and 50% of HC will become chronic hepatitis Acute hepatitis D:
Co-infection with HBV Super-infection with HBV

If women with pregnancy suffer from the HEfulminant hepatitis If HB super-infect HEV or HCVfulminant hepatitis Only appear in HBV, HCV and HDV infection

Mild chronic hepatitis

The course is more than half year Fatigue, dizziness, digestive tract symptoms, dull pain of liver, enlarged liver tenderness or spleen tenderness,lower degree of fever, ALT, the pathology change has only mild The course may persist many years

Moderate
The course half year The symptom are obvious Spider nevus, liver palms, hepatic face Dysfunction of liver Accompany the lesions of other organs and presence of autoantibody Reverse the ratio of albumin/globulin Biopsy show the changes of mild CAH

Severe
Except symptoms and signs mentioned, the biopsy show the changes of early cirrhosis and clinical manifestations of compensatory cirrhosis All of five kinds of hepatitis virus can cause this type of hepatitis. The incidence is only 0.2-0.5%, but the mortality is the highest.

Acute hepatitis gravis

The onset may begin in a typical acute icteric hepatitis, but within 10 days Jaundice deepens rapidly Vomit is frequent Obvious anorexia Hemorrhage The liver shrinks in size Toxic intestinal tympenice Prothrombin time is prolonged Ascites appear Acute renal failure Hepatic encephalopathy

Subacute hepatitis gravis

The course of AIH is more than 10 days The hepatic encephalupathy appear later The course may be several months The postnecrotic cirrhosis may develop

Chronic hepatitis gravis

Based on chronic hepatitis or cirrhosis developed subacute
hepatic necrotic

Cholestatic hepatitis
Intra hepatic cholestatic jaundice for a long time(2-4 months or longer) Pruritus Pale feces Hepatomogaly Subjective symptoms is slight Course 2-6 months Recovery is complete

Manifestations of hepatitis for special population

Characteristics of hepatitis for child Characteristics of hepatitis for the senility The character of hepatitis of pregnancy period

Laboratory examination Liver function

Serum transaminase ALT(alanine transferase) AST(aspartase transferase) ALP (Alkaline phosphatase) in chronic hepatitis LDH (Lactate dehydrogenase) Serum protein Albumin In chronic hepatitis Ig The ratio of A/G
Bilirubin Urobilinogen in early stage of AIH Urobilinogen and urobilin in icteric stage Urobilin is positive and urobilinogen may be negative in cholestatic hepatitis In AIH, the directive bilirubin and indirective bilirubin Prothrombin time may be prolonged especially in fulminant hepatitis Blood amonia examination

Detection of the markers of hepatitis virus

Hepatitis A

Serologic marker

Anti-HAVIgM: recent infection

Anti-HAVIgG: past infection HAV particles may be detected by RIA or IEM Isolation of HAV may use tissue culture or animal inoculation

Marker of feces

Hepatitis B Sero-immunologic marker

HBsAg HBcAg HBeAg

anti-HBs anti-HBc anti-Hbe

Molecular biological marker

DNAp HBV DNA Immune tissue chemistry examination

Hepatitis C Serological marker

Anti-HCVIgM Anti-HCVIgG

Molecular biologic marker

HCV RNA may be detective by RT-PCR 1-2 weeks after infection of HCV Quality of HCV RNA Immune tissue chemistry method detect HCAg within liver cells

Hepatitis D HDAg anti-HDV HDV RNA

Hepatitis E

Anti-HEVIgG,Anti-HEVIgm RT-PCR HEV particais: IF IEM

Ultra-sound examination Liver biopsy Other laboratory examination Blood routine Urine routine

Complication and prognosis

HB
Infection of biliary tract, pancreatitis, gastro-enteritis Diabetes Hemolytic anemia, aplastic anemia Myocarditis, polyarteritis, nodose Glomerulo-nephritis, renal tubular, acidosis Skin: allergic purpure Cirrhosis HCC

Diagnosis
Epidemiological data
HA, HE: food, water, seasonal, age HB, HC: blood and blood product transfusion, contact history, inoculation history

Clinical diagnosis Acute hepatitis Chronic hepatitis

HA: Serum anti-HAV IgM , Feces HAV HB: HBsAg HBeAg HBcAg anti-HBc HBVDNA DANp HC: anti-HCV IgM IgG HD: HBsAg HDAg anti-HDV HE: anti-HEV IgM IgG HEVRNA HEV particles in feces

Differential diagnosis Acute icteric hepatitis Must be differentiated with the jaundice caused by another
disease Hemolytic jaundice Extrahepatic obstructive jaundice

Hepatitis caused by another reasons

Toxic hepatitis Infective toxic hepatitis Mononucleosis Alcohol hepatic disease Schistosomiosis Wilson disease

Treatment
Acute hepatitis Isolation HA: 3 weeks after onset HB: HBsAg become negative HC: HCVRNA become negative HE: 2 weeks after onset

Rest Diet Anti-virus therapy

Chronic hepatitis Symptomatic therapy Diet Rest Hepatinice Supporting therapy Immunomodulator

Fuminant hepatitis General and supporting therapy

Rest: strict bed rest Diet Supporting therapy

Symptomatic therapy
Hemorrhage: fresh blood, prothrombin complex, platelet Hepatic encephalopathy

Prevention and treatment of amino poisoning Recovery normal neurotransmitter Sodium glutamate and arginine Treatment of cerebral edema Control infection Prevention and treatment of renal failure Promoting the growth of liver cells

Liver transplantation

Cholestatic hepatitis: Prevention

similar to acute hepatitis

Control of source of infection Cut off the route of transmission Protection of susceptible population

Active immunity Passive immunity